A young hepatologist once asked the medical pioneer Dame Sheila Sherlock, who has died aged 83, why she had chosen to work on liver disease. "Because no one else was doing it," she replied. Indeed, back in the 1940s when she started out, the specialty of hepatology did not exist; Sherlock was its main creator, and, in a glittering 60-year career, became one of the world's most famous names in clinical science.

As the first professor of medicine at London's Royal Free hospital school of medicine, she maintained its tradition of powerful and charismatic female pioneers. Under her leadership, the department became a focal point for trainees in hepatology from virtually every country, and many of today's leaders in the field spent part, or all, of their training under her. Her influence extended to colleagues in surgery, radiology and pathology, and many of them became liver specialists in their own fields.

Sherlock was also active nationally and internationally: in the Royal College of Physicians, as president of the British Society of Gastroenterology, as editor of Gut and the Journal of Hepatology, and as a founder - and later president - of the British Liver Trust, a national charity supporting liver research and patients with liver disease.

Born in Dublin and brought up in Folkestone, Sherlock attended Folkestone county school for girls. In prewar Britain, female applicants to medical schools were at a great disadvantage, and she was rejected by several colleges before gaining a place at Edinburgh University in 1936. Her outstanding abilities soon became obvious, however, and she graduated in 1941, only the second womanto be awarded the Ettles scholarship for finishing top of her year.

Professor Sir James Learmonth, her Edinburgh mentor, appointed her to an assistant lectureship in his department of surgery. In an autobiographical chapter in the anthology, My Medical School (edited by Dannie Abse, 1978), she explained how "Poppa" Learmonth taught her how to organise her results, write a paper and review the scientific literature.

After Edinburgh, Sherlock worked with Professor Sir John McMichael in the department of medicine at the Royal postgraduate school and Hammersmith hospital, first as medical research council fellow and Beit memorial research fellow, and later as lecturer and consultant. At Hammersmith, and as Rockefeller research fellow at Yale (1947-48), she studied the biochemistry and pathophysiology of liver disease.

Once appointed to the Royal Free in 1959, she had an important influence on the medical school's development and morale. In the 1940s and 1950s, when I was one of its first male students, the Royal Free was often perceived as a poor relation among London medical schools. Sherlock's reputation and drive changed this image radically. She was deeply loyal to her fellows and junior staff, and it is a tribute to the quality of her leadership and inspiration that many of them remained friends. She was the school's last president before it merged to become the Royal Free and University College medical school in 1998.

Retired from the chair of medicine in 1983, Sherlock continued to see patients, research and write. Her ability to give good lectures and teaching rounds was undiminished. Her exciting lectures kept everyone on their toes, because anyone in the audience might be asked for their opinion. Perhaps her greatest skill was her ability to discard the irrelevant and go straight to the heart of a question. This made her an unrivalled diagnostician.

She was also a clear and succinct writer, and her fellows and co-workers became accustomed to having their draft manuscripts returned covered in green ink, drastically shortened and very much improved. Her papers covered every aspect of liver disease, and she published more than 600 of them in scientific journals.

Perhaps her best-known book was Diseases Of The Liver And Biliary System (1955), which became popular because of its clarity and authority; now in its 11th edition, since 1993 it has been co-written with Dr James Dooley.

Modest and straightforward, more interested in her patients and in liver disease than in her many honours, Sherlock was, nevertheless, proud of her honorary degrees, of her DBE (1978) and of her election as a fellow of the Royal Society in 2001.

Throughout her career, she was ably supported by her distinguished physician husband, Dr Gerry James, who survives her, as do her two daughters, Amanda and Auriole.

· Sheila Patricia Violet Sherlock, physician and teacher, born March 31 1918; died December 30 2001